Defective Thymocyte Maturation in p44 MAP Kinase (Erk 1) Knockout Mice
Gilles Pagès,
1*
Sandrine Guérin,
2
Dominique Grall,
1
Frédéric Bonino,
1
Austin Smith,
3
Fabienne Anjuere,
2
Patrick Auberger,
2
Jacques Pouysségur
1*
The p42 and p44 mitogen-activated protein kinases (MAPKs),
also called Erk2 and Erk1, respectively, have been implicated in proliferation as well as in differentiation programs. The specific role
of the p44 MAPK isoform in the whole animal was evaluated by generation
of p44 MAPK-deficient mice by homologous recombination in embryonic
stem cells. The p44 MAPK-/- mice were viable, fertile,
and of normal size. Thus, p44 MAPK is apparently dispensable and p42
MAPK (Erk2) may compensate for its loss. However, in p44
MAPK
/ mice, thymocyte maturation beyond the
CD4+CD8+ stage was reduced by half, with a
similar diminution in the thymocyte subpopulation expressing high
levels of T cell receptor (CD3high). In p44
MAPK/ thymocytes, proliferation in response to
activation with a monoclonal antibody to the T cell receptor in the
presence of phorbol myristate acetate was severely reduced even though
activation of p42 MAPK was more sustained in these cells. The p44 MAPK
apparently has a specific role in thymocyte development.
1 Institute of Signaling, Developmental Biology
and Cancer Research, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue de
Valombrose, 06189 Nice, France.
2 Faculté de
Medecine, INSERM U364 and CJF 96.05, Avenue de Valombrose, 06107 Nice,
France.
3 Centre for Genome Research, King's
Building, West Mains Road, Edinburgh, Scotland, UK.
*
To whom correspondence should be addressed. E-mail:
gpages{at}unice.fr (G.P.) and pouysseg{at}unice.fr (J.P.)
